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综合蛋白质组学和连接性基于地图的分析揭示了在小鼠模型中对日本脑炎病毒感染具有潜在抗病毒作用的化合物

Rohit Soni¹, Naina Soni¹, Abhijit Paul²

¹Laboratory of Virology, Regional Centre for Biotechnology, Faridabad, India.

The FEBS journal

|December 23, 2024

概括

研究人员确定了两种有前途的药物,Ly303511和MDL11939,用于治疗日本脑炎病毒 (JEV) 感染. 这些针对宿主的化合物有效地降低了病毒载量,并改善了小鼠的生存率,为新的JEV疗法提供了希望.

科学领域:

神经科学是一个神经科学.
病毒学病毒学
药理学药理学是指药理学的学科.

背景情况:

日本脑炎病毒 (JEV) 是印度和南亚病毒性脑炎的主要原因.
迫切需要有效的抗病毒疗法来治疗JEV诱导的脑炎.
药物再利用为开发新疗法提供了一种实用和经济的方法.

研究的目的:

开发一种宿主导的治疗策略,用于JEV感染,使用计算药物重定位.
通过向宿主蛋白质,识别可以抑制JEV病变的现有药物.

主要方法:

在JEV感染的小鼠大脑中使用半定量蛋白质组学生成了动态蛋白质表达特征.
利用连接地图 (CMap) 分析来识别具有高负CMap分数的潜在药物候选者.
在JEV感染的细胞培养物和小鼠中评估了精选化合物 (Tipifarnib, Ly303511, MDL11939) 的抗病毒功效.

主要成果:

Ly303511和MDL11939显示出显著的抗病毒潜力,表现优于Tipifarnib.
口服Ly303511和MDL11939,单独或组合,改善了JEV感染小鼠的生存率和减少病毒载量.
药物治疗有效地降低了病毒载量,并逆转了宿主的抗病毒反应特征.

结论:

鉴定出Ly303511和MDL11939是对JEV感染的有前途的宿主向抑制剂.
与Ly303511和MDL11939的联合治疗显示出改善临床结果和减少JEV诱导的损害的潜力.
这些发现支持对Ly303511和MDL11939在JEV治疗临床研究中的进一步调查.

关键词:

在JEV中,JEV是抗病毒药物抗病毒药物连接地图连接地图药物重用是为了改变药物的用途.蛋白质基质的个人资料蛋白质基质的个人资料

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